There is an important need to stimulate hair growth for various conditions of alopecia. To achieve hair growth stimulation,biologically- active compounds must be delivered inside hair-follicle cells. Active compounds in principle can be also used to cause desired changes in hair color and appearance. The optimal way to identify such compounds and methods of their delivery into hair-follicle cells is to use appropriate in vitro systems which allow the study of a large variety of substances on an individual specimen. This is particularly the case in the gel- supported three-dimensional histoculture system we have developed (Hoffman, R.M. Cancer Cells 3, 86-92, 1991) that allows the intact growth and testing of all components of skin, including keratinocytes, dermal fibroblasts and hair-follicle cells, for a period of 10 days or more (Li, L., et al. Proc. Natl. Acad. Sci.-USA. 88, 1908-1912, 1991). Hair itself can grow on such skin cultures (Li, L. et al., manuscript in preparation). On the other hand, it is known that liposomes - spherical phospholipid vesicles with bilayer membrane structure - are considered as convenient means for the intracellular delivery of different substances - from low-molecular-weight drugs to DNA plasmids. It is proposed here, using the histoculture system and fluorescent-labeled compounds included into liposomes, to study liposome interactions with hair-follicle cells, to find the optimal compositions for cell binding, to include into liposomes of a given composition different low-molecular- weight and high-molecular-weight, water-soluble and water-insoluble compounds and to find the optimal conditions for the release of the liposomal content into hair-follicle cells. In Phase II, in vitro studies with model compounds will be performed to determine their effects on human skin culture in order to develop a commercial system for intra- follicle delivery of substances influencing hair growth, color and appearance. PROPOSED COMMERCIAL APPLICATION: Using native-state three-dimensional histoculture system of mouse and human skin as a model and liposomes of different size and composition as delivery vehicles, a system can be developed for influencing hair growth, color and appearance.